Open Access. Powered by Scholars. Published by Universities.®

Medical Sciences Commons

Open Access. Powered by Scholars. Published by Universities.®

2015

Biological Phenomena, Cell Phenomena, and Immunity

Institution
Keyword
Publication
Publication Type
File Type

Articles 1 - 30 of 48

Full-Text Articles in Medical Sciences

How The Manipulation Of The Ras Homolog Enriched In Striatum Alters The Behavioral And Molecular Progression Of Huntington’S Disease, Franklin A. Lee Dec 2015

How The Manipulation Of The Ras Homolog Enriched In Striatum Alters The Behavioral And Molecular Progression Of Huntington’S Disease, Franklin A. Lee

University of New Orleans Theses and Dissertations

Huntington’s disease is an incurable, progressive neurological disorder characterized by loss of motor control, psychiatric dysfunction, and eventual dystonia leading to death. Despite the fact that this disorder is caused by a mutation in one single gene, there is no cure. The mutant Huntingtin (mHtt) protein is expressed ubiquitously throughout the brain but frank cell death is limited to the striatum. Recent work has suggested that Rhes, Ras homolog enriched in striatum, which is selectively expressed in the striatum, may play a role in Huntington’s disease neuropathology. In vitro studies have shown Rhes to be an E3 ligase for the …


Regulatory Roles Of Mical-L1 And Ehd1 In Cell Signaling And Mitosis, James B. Reinecke Dec 2015

Regulatory Roles Of Mical-L1 And Ehd1 In Cell Signaling And Mitosis, James B. Reinecke

Theses & Dissertations

Membrane trafficking is a basic cell biological process that controls the distribution of proteins and lipids. Our lab is particularly interested in delineating the cellular functions as well as the molecular mechanisms that regulate the C-terminal Eps15 Homology Domain (EHD) protein family of adenosine-5’-triphosphatases in mammalian cells. EHD1-4 are ubiquitously expressed in mammalian tissues and serve partially overlapping but also distinct functions in regulating membrane shaping and fission along the endocytic pathway. Specifically, EHD1 is recruited to tubular recycling endosomes (TREs) by Molecule Interacting with CasL Like-1 (MICAL-L1) and facilitates TRE fission and release of cargo from the perinuclear endocytic …


Role Of Stat3 In Human Nk Cell Functions, Prasad V. Phatarpekar Dec 2015

Role Of Stat3 In Human Nk Cell Functions, Prasad V. Phatarpekar

Dissertations & Theses (Open Access)

Natural Killer (NK) cells are cytotoxic lymphocytes, which play a critical role in the immune response against malignant cells and microbial infections. NK cells are equipped with activating receptors, which upon detecting ligands expressed on stressed cells induce cytolytic activity of NK cells. Stimulation of NK cell proliferation and priming of NK cytolytic capability are accomplished by cytokines, which mediate their signals mainly through JAK-STAT signaling pathway. Previously, we found that K562 cells genetically modified to express membrane bound IL-21 (mbIL-21), which predominantly activates STAT3, induce robust expansion and activation of human NK cells. Further investigations revealed role of STAT3 …


Does The Expression Of Ki-67, P16 And Cox-2 At Initial Diagnosis Of Breast Atypia Or Usual Ductal Hyperplasia Predict A Second Clinically Significant Event?, Judy A. Tjoe, Philippe Gascard, Jianxin Zhao, Gary F. Neitzel, Maharaj Singh, Brittany Last, James Marx, Thea Tlsty, Sanjay Kansra Nov 2015

Does The Expression Of Ki-67, P16 And Cox-2 At Initial Diagnosis Of Breast Atypia Or Usual Ductal Hyperplasia Predict A Second Clinically Significant Event?, Judy A. Tjoe, Philippe Gascard, Jianxin Zhao, Gary F. Neitzel, Maharaj Singh, Brittany Last, James Marx, Thea Tlsty, Sanjay Kansra

Journal of Patient-Centered Research and Reviews

Background: Women diagnosed with atypical ductal hyperplasia (ADH) or atypical lobular hyperplasia (ALH) have a fivefold increased risk of developing breast cancer. Because ADH/ALH can be precursors or predictive markers of a subsequent clinically significant event (SCSE), i.e. atypia, in situ or invasive carcinoma, the clinical outcome for these patients ranges anywhere from remission to invasive malignancy. Currently we cannot predict which atypical breast lesion is likely to be associated with future cancer, resulting in aggressive management and, possibly, overtreatment. Kerlikowske et al. reported that a combination of three biomarkers (cell cycle regulator p16INK4a, proliferation antigen Ki-67 and stress response …


Identification Of Hydroxyxanthones As Na/K-Atpase Ligands, Zhongbing Zhang, Zhichuan Li, Jiang Tian, Wei Jiang, Yin Wang, Xiaojin Zhang, Zhuorong Li, Qidong You, Joseph Shapiro, Shuyi Si, Zijian Xie Oct 2015

Identification Of Hydroxyxanthones As Na/K-Atpase Ligands, Zhongbing Zhang, Zhichuan Li, Jiang Tian, Wei Jiang, Yin Wang, Xiaojin Zhang, Zhuorong Li, Qidong You, Joseph Shapiro, Shuyi Si, Zijian Xie

Zijian Xie

We have screened a chemical library and identified several novel structures of Na/K-ATPase inhibitors. One group of these inhibitors belongs to polyphenolic xanthone derivatives. Functional characterization reveals the following properties of this group of inhibitors. First, like ouabain, they are potent inhibitors of the purified Na/K-ATPase. Second, their effects on the Na/K-ATPase depend on the number and position of phenolic groups. Methylation of these phenolic groups reduces the inhibitory effect. Third, further characterization of the most potent xanthone derivative, MB7 (3,4,5,6-tetrahydroxyxanthone), reveals that it does not change either Na+ or ATP affinity of the enzyme. Finally, unlike that of …


Marinobufagenin Stimulates Fibroblast Collagen Production And Causes Fibrosis In Experimental Uremic Cardiomyopathy, Jihad Elkareh, David Kennedy, Belvadi Yashaswi, Sandeep Vetteth, Amjad Shidyak, Eric Kim, Sleiman Smaili, Sankaridrug Periyasamy, Imad Hariri, Larisa Fedorova, Jiang Liu, Liang Wu, M. Kahaleh, Zijian Xie, Deepak Malhotra, Olga Fedorova, Vladimir Kashkin, Alexei Bagrov, Joseph Shapiro Sep 2015

Marinobufagenin Stimulates Fibroblast Collagen Production And Causes Fibrosis In Experimental Uremic Cardiomyopathy, Jihad Elkareh, David Kennedy, Belvadi Yashaswi, Sandeep Vetteth, Amjad Shidyak, Eric Kim, Sleiman Smaili, Sankaridrug Periyasamy, Imad Hariri, Larisa Fedorova, Jiang Liu, Liang Wu, M. Kahaleh, Zijian Xie, Deepak Malhotra, Olga Fedorova, Vladimir Kashkin, Alexei Bagrov, Joseph Shapiro

Jiang Liu

We have observed recently that experimental renal failure in the rat is accompanied by increases in circulating concentrations of the cardiotonic steroid, marinobufagenin (MBG), and substantial cardiac fibrosis. We performed the following studies to examine whether MBG might directly stimulate cardiac fibroblast collagen production. In vivo studies were performed using the 5/6th nephrectomy model of experimental renal failure (PNx), MBG infusion (MBG), PNx after immunization against MBG, and concomitant PNx and adrenalectomy. Physiological measurements with a Millar catheter and immunohistochemistry were performed. In vitro studies were then pursued with cultured isolated cardiac fibroblasts. We observed that PNx and MBG increased …


Marinobufagenin Stimulates Fibroblast Collagen Production And Causes Fibrosis In Experimental Uremic Cardiomyopathy, Jihad Elkareh, David Kennedy, Belvadi Yashaswi, Sandeep Vetteth, Amjad Shidyak, Eric Kim, Sleiman Smaili, Sankaridrug Periyasamy, Imad Hariri, Larisa Fedorova, Jiang Liu, Liang Wu, M. Kahaleh, Zijian Xie, Deepak Malhotra, Olga Fedorova, Vladimir Kashkin, Alexei Bagrov, Joseph Shapiro Sep 2015

Marinobufagenin Stimulates Fibroblast Collagen Production And Causes Fibrosis In Experimental Uremic Cardiomyopathy, Jihad Elkareh, David Kennedy, Belvadi Yashaswi, Sandeep Vetteth, Amjad Shidyak, Eric Kim, Sleiman Smaili, Sankaridrug Periyasamy, Imad Hariri, Larisa Fedorova, Jiang Liu, Liang Wu, M. Kahaleh, Zijian Xie, Deepak Malhotra, Olga Fedorova, Vladimir Kashkin, Alexei Bagrov, Joseph Shapiro

Zijian Xie

We have observed recently that experimental renal failure in the rat is accompanied by increases in circulating concentrations of the cardiotonic steroid, marinobufagenin (MBG), and substantial cardiac fibrosis. We performed the following studies to examine whether MBG might directly stimulate cardiac fibroblast collagen production. In vivo studies were performed using the 5/6th nephrectomy model of experimental renal failure (PNx), MBG infusion (MBG), PNx after immunization against MBG, and concomitant PNx and adrenalectomy. Physiological measurements with a Millar catheter and immunohistochemistry were performed. In vitro studies were then pursued with cultured isolated cardiac fibroblasts. We observed that PNx and MBG increased …


Spironolactone Attenuates Experimental Uremic Cardiomyopathy By Antagonizing Marinobufagenin, Jiang Tian, Amjad Shidyak, Sankaridrug Periyasamy, Steven Haller, Mohamed Taleb, Nasser El-Okdi, Jihad Elkareh, Shalini Gupta, Sabry Gohara, Olga Fedorova, Christopher Cooper, Zijian Xie, Deepak Malhorta, Alexei Bagrov, Joseph Shapiro Sep 2015

Spironolactone Attenuates Experimental Uremic Cardiomyopathy By Antagonizing Marinobufagenin, Jiang Tian, Amjad Shidyak, Sankaridrug Periyasamy, Steven Haller, Mohamed Taleb, Nasser El-Okdi, Jihad Elkareh, Shalini Gupta, Sabry Gohara, Olga Fedorova, Christopher Cooper, Zijian Xie, Deepak Malhorta, Alexei Bagrov, Joseph Shapiro

Zijian Xie

Spironolactone has been noted to attenuate cardiac fibrosis. We have observed that the cardiotonic steroid marinobufagenin plays an important role in the diastolic dysfunction and cardiac fibrosis seen with experimental renal failure. We performed the following studies to determine whether and how spironolactone might ameliorate these changes. First, we studied rats subjected to partial nephrectomy or administration of exogenous marinobufagenin. We found that spironolactone (20 mg/kg per day) attenuated the diastolic dysfunction as assessed by ventricular pressure-volume loops and essentially eliminated cardiac fibrosis as assessed by trichrome staining and Western blot. Next, we examined the effects of spironolactone and its …


Marinobufagenin Induces Increases In Procollagen Expression In A Process Involving Protein Kinase C And Fli-1: Implications For Uremic Cardiomyopathy, Jihad Elkareh, Sankaridrug Periyasamy, Amjad Shidyak, Sandeep Vetteth, Jeremy Schroeder, Vanamala Raju, Imad Hariri, Nasser El-Okdi, Shalini Gupta, Larisa Fedorova, Jiang Liu, Olga Fedorova, M. Kahaleh, Zijian Xie, Deepak Malhotra, Dennis Watson, Alexei Bagrov, Joseph Shapiro Sep 2015

Marinobufagenin Induces Increases In Procollagen Expression In A Process Involving Protein Kinase C And Fli-1: Implications For Uremic Cardiomyopathy, Jihad Elkareh, Sankaridrug Periyasamy, Amjad Shidyak, Sandeep Vetteth, Jeremy Schroeder, Vanamala Raju, Imad Hariri, Nasser El-Okdi, Shalini Gupta, Larisa Fedorova, Jiang Liu, Olga Fedorova, M. Kahaleh, Zijian Xie, Deepak Malhotra, Dennis Watson, Alexei Bagrov, Joseph Shapiro

Zijian Xie

The cardiotonic steroid marinobufagenin (MBG) has been implicated in the pathogenesis of experimental uremic cardiomyopathy, which is characterized by progressive cardiac fibrosis. We examined whether the transcription factor Friend leukemia integration-1 (Fli-1) might be involved in this process. Fli-1-knockdown mice demonstrated greater cardiac collagen-1 expression and fibrosis compared with wild-type mice; both developed increased cardiac collagen expression and fibrosis after 5/6 nephrectomy. There was a strong inverse relationship between the expressions of Fli-1 and procollagen in primary culture of rat cardiac and human dermal fibroblasts as well as a cell line derived from renal fibroblasts and MBG-induced decreases in nuclear …


Prieurianin Causes Weight Loss In Diet-Induced Obese Mice And Inhibits Adipogenesis In Cultured Preadipocytes, Ahmed Kablan, Rudel A. Saunders, Maria Szkudlarek-Mikho, Andrew J.B. Chin, Raul M. Bosio, Kazuyuki Fujii, Joseph I. Shapiro M.D., Khew-Voon Chin Sep 2015

Prieurianin Causes Weight Loss In Diet-Induced Obese Mice And Inhibits Adipogenesis In Cultured Preadipocytes, Ahmed Kablan, Rudel A. Saunders, Maria Szkudlarek-Mikho, Andrew J.B. Chin, Raul M. Bosio, Kazuyuki Fujii, Joseph I. Shapiro M.D., Khew-Voon Chin

Joseph I Shapiro MD

The global increase in the incidence of obesity has emerged as one of the most serious public health risks in recent years. Despite the enormity of the obesity pandemic, there are currently only two FDA-approved therapies for its treatment and these drugs exhibit modest effi cacy and have limiting side effects. Prieurianin is a plant limonoid product that deters feeding in insect larvae. We investigated in this study the effects of prieurianin on weight loss and adipogenesis. Our results showed that prieurianin causes weight loss by reducing energy intake in obese mice on highcalorie diet. We also found that prieurianin …


Down-Regulation Of The Transcription Factor Snail In The Placentas Of Patients With Preeclampsia And In A Rat Model Of Preeclampsia, Larissa Federova, Cara Gatto-Weis, Sleiman Smaili, Nauman Khurshid, Joseph I. Shapiro M.D., Deepak Malhorta, Terrence Horrigan Sep 2015

Down-Regulation Of The Transcription Factor Snail In The Placentas Of Patients With Preeclampsia And In A Rat Model Of Preeclampsia, Larissa Federova, Cara Gatto-Weis, Sleiman Smaili, Nauman Khurshid, Joseph I. Shapiro M.D., Deepak Malhorta, Terrence Horrigan

Joseph I Shapiro MD

Background: Placental malfunction in preeclampsia is believed to be a consequence of aberrant differentiation of trophoblast lineages and changes in utero-placental oxygenation. The transcription factor Snail, a master regulator molecule of epithelial-mesenchymal transition in embryonic development and in cancer, is shown to be involved in trophoblast differentiation as well. Moreover, Snail can be controlled by oxidative stress and hypoxia. Therefore, we examined the expression of Snail and its downstream target, e-cadherin, in human normal term, preterm and preeclamptic placentas, and in pregnant rats that developed preeclampsia-like symptoms in the response to a 20- fold increase in sodium intake. Methods: Western …


Stem Cell Transplantation Increases Antioxidant Effects In Diabetic Mice, Ming Li, Luca Vanella, Yuming Zhang, Ming Shi, Takashi Takaki, Joseph I. Shapiro M.D., Susuma Ikehera Sep 2015

Stem Cell Transplantation Increases Antioxidant Effects In Diabetic Mice, Ming Li, Luca Vanella, Yuming Zhang, Ming Shi, Takashi Takaki, Joseph I. Shapiro M.D., Susuma Ikehera

Joseph I Shapiro MD

Intra bone marrow-bone marrow transplantation (IBM- BMT) + thymus transplantation (TT) has been shown to reduce the incidence of graft versus host disease (GVHD) and restore donor-derived T cell function. In addition, an increase in insulin sensitivity occurred in db/db mice after IBM-BMT+TT treatment. Heme oxygenase (HO)-1 is a stress inducible enzyme which exert antioxidant, antiapoptotic, and immune-modulating properties. We examined whether IBM-BMT+TT could modulate the expression of HO-1 in the kidneys of db/db mice. Six-week-old db/db mice with blood glucose levels higher than 250 mg/dl were treated with IBM-BMT+TT. Six weeks later, the db/db mice showed decreased body weight, …


Ouabain Decreases Sarco(Endo)Plasmic Reticulum Calcium Atpase Activity In Rat Hearts By A Process Involving Protein Oxidation, David Kennedy, Sandeep Vetteth, Miaorong Xie, Sankaridrug Periyasamy, Jingwei Xie, Chi Han, Venkatesha Basrur, Krishna Mutgi, Vladimir Fedorov, Deepak Malhotra, Joseph Shapiro Sep 2015

Ouabain Decreases Sarco(Endo)Plasmic Reticulum Calcium Atpase Activity In Rat Hearts By A Process Involving Protein Oxidation, David Kennedy, Sandeep Vetteth, Miaorong Xie, Sankaridrug Periyasamy, Jingwei Xie, Chi Han, Venkatesha Basrur, Krishna Mutgi, Vladimir Fedorov, Deepak Malhotra, Joseph Shapiro

Jingwei Xie

The effect of cardiac glycosides to increase cardiac inotropy by altering Ca2+ cycling is well known but still poorly understood. The studies described in this report focus on defining the effects of ouabain signaling on sarcoplasmic reticulum Ca2+-ATPase function. Rat cardiac myocytes treated with 50 μM ouabain demonstrated substantial increases in systolic and diastolic Ca2+ concentrations. The recovery time constant for the Ca2+ transient, τ, was significantly prolonged by ouabain. Exposure to 10 μM H2O2, which causes an increase in intracellular reactive oxygen species similar to that of 50 μM ouabain, caused a similar increase in τ. Concurrent exposure to …


Effects Of Cardiotonic Steroids On Dermal Collagen Synthesis And Wound Healing, Nasser El-Okdi, Sleiman Smaili, Vanamala Raju, Amjad Shidyak, Shalini Gupta, Larisa Fedorova, Jihad Elkareh, Sankaridrug Periyasamy, Anna Shapiro, M. Kahaleh, Deepak Malhotra, Jingwei Xie, Khew Chin, Joseph Shapiro Sep 2015

Effects Of Cardiotonic Steroids On Dermal Collagen Synthesis And Wound Healing, Nasser El-Okdi, Sleiman Smaili, Vanamala Raju, Amjad Shidyak, Shalini Gupta, Larisa Fedorova, Jihad Elkareh, Sankaridrug Periyasamy, Anna Shapiro, M. Kahaleh, Deepak Malhotra, Jingwei Xie, Khew Chin, Joseph Shapiro

Jingwei Xie

We previously reported that cardiotonic steroids stimulate collagen synthesis by cardiac fibroblasts in a process that involves signaling through the Na-K-ATPase pathway (Elkareh et al. Hypertension 49: 215–224, 2007). In this study, we examined the effect of cardiotonic steroids on dermal fibroblasts collagen synthesis and on wound healing. Increased collagen expression by human dermal fibroblasts was noted in response to the cardiotonic steroid marinobufagenin in a dose- and time-dependent fashion. An eightfold increase in collagen synthesis was noted when cells were exposed to 10 nM marinobufagenin for 24 h (P < 0.01). Similar increases in proline incorporation were seen following treatment with digoxin, ouabain, and marinobufagenin (10 nM × 24 h, all results P < 0.01 vs. control). The coadministration of the Src inhibitor PP2 or N-acetylcysteine completely prevented collagen stimulation by marinobufagenin. …


The Role Of Glutaminase 1 In Hiv-1 Associated Neurocognitive Disorders And In Brain Development, Yi Wang Aug 2015

The Role Of Glutaminase 1 In Hiv-1 Associated Neurocognitive Disorders And In Brain Development, Yi Wang

Theses & Dissertations

Glutaminase is the enzyme that converts glutamine into glutamate, which serves as a key excitatory neurotransmitter and one of the energy providers for cellular metabolism. Glutamate is essential for proper brain functioning but at excess levels, it is neurotoxic and has a key role in the pathogenesis of various neurodegenerative diseases, including HIV-1 associated neurocognitive disorders (HAND). However, the detailed mechanism of glutamate-mediated neurotoxicity remains unclear. In part I, we identified the regulation of glutaminase 1 (GLS1) in the central nervous system (CNS) of HAND animal models including HIV-Tat transgenic (Tg) mouse and HIVE-SCID mouse, since GLS1 is the dominant …


Characterization Of The Nicotine-Induced Endoplasmic Reticulum Stress Response In The Rat Placenta In Vivo And In Vitro, Michael Ka Chun Wong Aug 2015

Characterization Of The Nicotine-Induced Endoplasmic Reticulum Stress Response In The Rat Placenta In Vivo And In Vitro, Michael Ka Chun Wong

Electronic Thesis and Dissertation Repository

Nicotine exposure during pregnancy leads to adverse health outcomes, including compromised placental development. Although the molecular mechanisms remain elusive, recent studies identified that endoplasmic reticulum (ER) stress may underlie poor placentation. Therefore, we were interested in investigating the effects of nicotine exposure on the ER stress response in the placenta. A well-established maternal nicotine exposure rat model and Rcho-1 trophoblast giant cell model were utilized to address the research questions. Maternal nicotine exposure in vivo led to elevated ER stress in association with impaired disulfide bond formation and hypoxia. Nicotine exposure in vitro further differentiated that ER stress may be …


Differential Microglial Activation Following Immune Challenge In Peripubertal And Adult Outbred Mice, David J. Placzek Jul 2015

Differential Microglial Activation Following Immune Challenge In Peripubertal And Adult Outbred Mice, David J. Placzek

Masters Theses

Pubertal development is a time of growth and development in the brain, leading to high sensitivity during this period. Past research in our lab has shown that shipping female inbred and outbred mice during pubertal development alters their sensitivity to steroid hormones in adulthood, thus affecting sexual receptivity, cognition, depression-like behavior, and anxiety-like behavior. Here, we test the hypothesis that mice treated with lipopolysaccharide during pubertal development would have more active microglia, the brain's immune cells, after injection than mice treated with lipopolysaccharide in adulthood. No significant interactions were observed between treatment and age between any brain area measured, suggesting …


Using Lectinmicroarrays To Identify Regulatory Mechanisms For Mammalian Glycosylation, John F. Rakus Jul 2015

Using Lectinmicroarrays To Identify Regulatory Mechanisms For Mammalian Glycosylation, John F. Rakus

John F. Rakus

Glycosylation involves the post-translational addition of carbohydrates to protein molecules and is an intricate and indispensable biochemical process. Study of this complicated network of interactions is hindered by the lack of a coding template analogous to the genetic code, and by the vast structural complexity inherent to carbohydrate polymers. We use lectins (non-enzymatic carbohydrate-binding proteins of non-immunological origin) as microarray probes to identify carbohydrate features expressed on cellular surfaces. Specifically, we utilized lectin microarray technology to investigate the differences in carbohydrates expressed by the cell lines of the Nation Cancer Institute’s NCI-60 panel. Our investigation identified tissue-specific expression differences in …


Dna-Pkcs-Mediated Transcriptional Regulation Drives Prostate Cancer Progression And Metastasis., Jonathan F Goodwin, Vishal Kothari, Justin M Drake, Shuang Zhao, Emanuela Dylgjeri, Jeffry L. Dean, Matthew J. Schiewer, Christopher Mcnair, Jennifer K. Jones, Alvaro Aytes, Michael S. Magee, Adam E. Snook, Ziqi Zhu, Robert Den, Ruth C. Birbe, Leonard G. Gomella, Nicholas A. Graham, Ajay A. Vashisht, James A. Wohlschlegel, Thomas G. Graeber, R. Jeffrey Karnes, Mandeep Takhar, Elai Davicioni, Scott A. Tomlins, Cory Abate-Shen, Nima Sharifi, Owen N. Witte, Felix Y. Feng, Karen E. Knudsen Jul 2015

Dna-Pkcs-Mediated Transcriptional Regulation Drives Prostate Cancer Progression And Metastasis., Jonathan F Goodwin, Vishal Kothari, Justin M Drake, Shuang Zhao, Emanuela Dylgjeri, Jeffry L. Dean, Matthew J. Schiewer, Christopher Mcnair, Jennifer K. Jones, Alvaro Aytes, Michael S. Magee, Adam E. Snook, Ziqi Zhu, Robert Den, Ruth C. Birbe, Leonard G. Gomella, Nicholas A. Graham, Ajay A. Vashisht, James A. Wohlschlegel, Thomas G. Graeber, R. Jeffrey Karnes, Mandeep Takhar, Elai Davicioni, Scott A. Tomlins, Cory Abate-Shen, Nima Sharifi, Owen N. Witte, Felix Y. Feng, Karen E. Knudsen

Department of Cancer Biology Faculty Papers

Emerging evidence demonstrates that the DNA repair kinase DNA-PKcs exerts divergent roles in transcriptional regulation of unsolved consequence. Here, in vitro and in vivo interrogation demonstrate that DNA-PKcs functions as a selective modulator of transcriptional networks that induce cell migration, invasion, and metastasis. Accordingly, suppression of DNA-PKcs inhibits tumor metastases. Clinical assessment revealed that DNA-PKcs is significantly elevated in advanced disease and independently predicts for metastases, recurrence, and reduced overall survival. Further investigation demonstrated that DNA-PKcs in advanced tumors is highly activated, independent of DNA damage indicators. Combined, these findings reveal unexpected DNA-PKcs functions, identify DNA-PKcs as a potent driver …


Investigating The Role Of Hydrogen Sulfide In The Survival, Growth And Angiogenic Potential Of Clear Cell Renal Cell Carcinoma Cell Lines And Xenografts, Eric Sonke Jun 2015

Investigating The Role Of Hydrogen Sulfide In The Survival, Growth And Angiogenic Potential Of Clear Cell Renal Cell Carcinoma Cell Lines And Xenografts, Eric Sonke

Electronic Thesis and Dissertation Repository

Clear cell renal cell carcinoma (ccRCC) is characterized by Von Hippel-Lindau (VHL)-deficiency, resulting in pseudohypoxic, angiogenic and glycolytic tumours. Hydrogen sulfide (H2S) is an endogenously-produced gasotransmitter that accumulates under hypoxia and has been shown to be pro-angiogenic and cytoprotective in cancer. It was hypothesized that H2S levels are elevated in VHL-deficient ccRCC, contributing to survival, metabolism, and angiogenesis. Using H2S-specific probes, it was found that H2S levels were higher in VHL-deficient ccRCC cell lines compared to cells with wild-type VHL. Inhibition of H2S-producing enzymes could reduce the proliferation, metabolism …


Functional Analysis Of The Molluscum Contagiosum Virus Mc160 Death Effector Domain-Containing Protein Rxdl Motif, Sarah Weber May 2015

Functional Analysis Of The Molluscum Contagiosum Virus Mc160 Death Effector Domain-Containing Protein Rxdl Motif, Sarah Weber

Seton Hall University Dissertations and Theses (ETDs)

The Molluscum contagiosum virus (MCV) is a member of the Poxviridae family that causes benign skin lesions. MCV lesions persist on average for 8-12 months in otherwise healthy individuals. MCV lesions are characterized by reduced inflammation. The persistence and reduction of inflammation at the site of MCV lesions have been attributed to MCV immune evasion genes. MCV encodes two death effector domain (DED) containing proteins, MC159 and MC160. DEDs are found in cellular proteins such as FADD and procaspase-8. These cellular proteins are involved in several innate immune responses such as apoptosis and activation of interferon (IFN). Presumably, MC159 and …


Qualitatively Assessing The Expression Of Kynurenine Pathway Metabolic Enzymes In Human Glioma Tissue, Kaushik Varadarajan May 2015

Qualitatively Assessing The Expression Of Kynurenine Pathway Metabolic Enzymes In Human Glioma Tissue, Kaushik Varadarajan

Honors College Theses

Gliomas are the most common brain tumor and glioblastoma multiforme (GBM) is the most common type of glioma observed in patients. Prognosis with late stage glioma and GBM is very poor even with recent advances in treatment. Along with treating the tumor, manners of bypassing the blood brain barrier and ensuring the tumor uptakes the treatment is necessary. Because the treatments can harm regular brain cells there is concern about the viability and toxic side effects of many treatments. With all of these challenges posed it is important to understand how glial tumors can be so recurring and difficult to …


Cannabinoid-Mediated Epigenetic Regulation Of Immune Functions, Jessica Margaret Sido May 2015

Cannabinoid-Mediated Epigenetic Regulation Of Immune Functions, Jessica Margaret Sido

Theses and Dissertations

The cannabinoid system consisting of exogenous and endogenous ligands as well as dedicated receptors has been proposed to play a regulatory role in immune functions. The exogenous cannabinoid Δ9-tetrahydrocannabinol (THC), one of the most widely studied marijuana derivatives, has been associated with multiple anti-inflammatory properties over the years. The majority of THC research has centered on the shift from Th1 to Th2 responses however, the complexity of inflammation has since increased. Recent studies have revealed that epigenome, Th cell subsets, and immunoregulatory cell induction, are all known to impact inflammation. In the current research, we have attempted to look holistically …


Use Of Immunotherapy In The Treatment Of Peanut Allergies In The Pediatric Population, Bethany Rauscher May 2015

Use Of Immunotherapy In The Treatment Of Peanut Allergies In The Pediatric Population, Bethany Rauscher

Senior Honors Theses

Peanut allergies are a serious issue that must be monitored and treated effectively to avoid severe adverse effects and death. In the last decade, their incidence has increased significantly, due to indeterminate factors. Because people typically do not outgrow peanut allergies and the effects of exposure can be life-threatening, it is important that a cure or management method is developed and refined. Recent research regarding treatment for peanut allergies has focused on the use of immunotherapy, a process aimed at desensitizing children's immune systems so that they do not reject foods that contain peanuts. Some studies utilizing immunotherapy have provided …


Correlation Matrix Analysis Identifies Gene Signatures Of Immune Cell Subsets And Their Interactions In Follicular Lymphoma, Jason R. Westin May 2015

Correlation Matrix Analysis Identifies Gene Signatures Of Immune Cell Subsets And Their Interactions In Follicular Lymphoma, Jason R. Westin

Dissertations & Theses (Open Access)

There are important but ill-defined interactions between benign immune cell subsets and neoplastic B cells within follicular lymphoma (FL). Using the novel technique of correlation matrix analysis (CMA) of publicly available FL whole-tumor gene expression profiling (GEP) data, we have identified signatures of immune cell subsets. Overall survival correlated most highly with a model using signatures of macrophages, T cells, and stroma, which was able to add significantly to existing clinical prognostic tools. From our own data of a cohort of 43 FL tumors sorted into B-cell and non-B cell (NB) fractions for GEP, CMA of the tumor infiltrating NB …


The Use Of Shape Memory Polymers As A Tool To Study Human Fibrosarcoma And Murine Mesenchymal Stem Cell Migration, Justin N. Elkhechen May 2015

The Use Of Shape Memory Polymers As A Tool To Study Human Fibrosarcoma And Murine Mesenchymal Stem Cell Migration, Justin N. Elkhechen

Honors Capstone Projects - All

Shape memory polymers (SMPs) are a class of “smart” materials that can transform between two distinct conformations through external stimuli, such as heat or electricity. Their usage in bioengineering has led to a promising field of research that lies at the interface of cell and mechanobiology, potentially providing insight into cancer therapies and tissue development—two processes that exist in dynamic environments in vivo. The present work involves creating new, shape changing, scaffolds for studies to analyze cell migration upon changes to the environmental topography. Specifically, this Capstone has been primarily focused on the development of a “half and half” fibrous …


Protective Effect Of Modified Human Fibroblast Growth Factor On Diabetic Nephropathy, Ana M. Pena Diaz Apr 2015

Protective Effect Of Modified Human Fibroblast Growth Factor On Diabetic Nephropathy, Ana M. Pena Diaz

Electronic Thesis and Dissertation Repository

Oxidative stress is a key mechanism causing Diabetic Nephropathy (DN). Acidic fibroblast growth factor (aFGF) is known to confer protection from oxidative stress. However, it also has significant angiogenic activity. Hence, we have generated a mutated human acidic FGF (maFGF), with intact antioxidant properties but devoid of angiogenic activities. Recent evidence shows that maFGF treatment prevented diabetic cardiomyopathy and further in vitro studies suggest that this prevention is mediated by suppression of cardiac oxidative stress, hypertrophy and fibrosis. We hypothesized that maFGF treatment has a protective effect in DN.

We show that maFGF treatment did not affect body weight and …


Iron Alters Cell Survival In A Mitochondria-Dependent Pathway In Ovarian Cancer Cells., Edward Haller Feb 2015

Iron Alters Cell Survival In A Mitochondria-Dependent Pathway In Ovarian Cancer Cells., Edward Haller

Edward Haller

ABSTRACT The role of iron in the development of cancer remains unclear. We previously reported that iron reduces cell survival in a Ras/mitogen-activated protein kinase (MAPK)-dependent manner in ovarian cells; however, the underlying downstream pathway leading to reduced survival was unclear. Although levels of intracellular iron, ferritin/CD71 protein and reactive oxygen species did not correlate with iron-induced cell survival changes, we identified mitochondrial damage (via TEM) and reduced expression of outer mitochondrial membrane proteins (translocase of outer membrane: TOM20 and TOM70) in cell lines sensitive to iron. Interestingly, Ru360 (an inhibitor of the mitochondrial calcium uniporter) reversed mitochondrial changes and …


Human Stem Cells: Is It Possible To Limit Pluripotent Human Stem Cells To Differentiate Into Specific Tissue Or Organ?, Chaya Korf Jan 2015

Human Stem Cells: Is It Possible To Limit Pluripotent Human Stem Cells To Differentiate Into Specific Tissue Or Organ?, Chaya Korf

The Science Journal of the Lander College of Arts and Sciences

It would seem that differentiation of stem cells is the remedy of modern times. Yet stem cell research is more complex that the public may recognize and is still in the developmental stage. Recent breakthroughs show promise; various guidelines provide structure to this growing field but it is not ready for gross public application. The objective of this paper is to research various different methods of stem cell production and application. Methods included reviewing articles and studies to evaluate the process in production of affective stem cells. There are many therapies that illustrate this research. Upon completing and explaining this …


Crf07_Bc Strain Dominates The Hiv-1 Epidemic In Injection Drug Users In Liangshan Prefecture Of Sichuan, China, Lin Li, Daying Wei, Wan-Ling Hsu, Tianyi Li, Tao Gui, Charles Wood, Yongjian Liu, Hanping Li, Zuoyi Bao, Siyang Liu, Xiaolin Wang, Jingyun Li Jan 2015

Crf07_Bc Strain Dominates The Hiv-1 Epidemic In Injection Drug Users In Liangshan Prefecture Of Sichuan, China, Lin Li, Daying Wei, Wan-Ling Hsu, Tianyi Li, Tao Gui, Charles Wood, Yongjian Liu, Hanping Li, Zuoyi Bao, Siyang Liu, Xiaolin Wang, Jingyun Li

Nebraska Center for Virology: Faculty Publications

The Liangshan prefecture in Sichuan province is an area in China severely affected by the HIV epidemic, with intravenous drug use (IDU) as the main risk factor. No reports on HIV subtypes prevalent in IDUs in Liangshan prefecture could be found. In this study, we have characterized the genotypes of HIV-1 in the IDU population in Liangshan prefecture and further determined the phylogenetic relationship of the CRF07_BC strains to HIV-1 sequences from the other regions of China, including Xinjiang and Yunnan provinces, to explore the pattern and possible diffusion pathway of HIV-1 in these regions. HIV-1-seropositive drug-naive IDUs identified in …